Autism Spectrum Disorders (ASD) are severe, life-long neurodevelopmental disorders that confer considerable impairment to individuals as well as a substantial burden to their families. Little is known about the prevalence or correlates of ASD. Little high quality information is available regarding the phenotypic variation among individuals with ASD, prevalence of co-morbid conditions, and risk factors that might be related to the development of ASD. The Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) were established in 2001 to investigate causes and correlates of autism. The focus of this second funding cycle is to conduct a multi-site collaborative epidemiologic study to investigate risk and causal factors for ASD and phenotypic subgroups of ASD using a population-based case-cohort study design. Six sites (California, Maryland, North Carolina, Pennsylvania, Colorado, and Georgia) will collaborate to enroll 2700 children and their families over the 5-year study period. Each site will include approximately 150 children with ASD, 150 with other neurodevelopmental disorders, and 150 general population controls to address specific hypotheses in six broad domains: 1) phenotypic variation in ASD, including the pattern of clustering of core symptoms, timing of onset, cognitive status, and presence of medical and psychiatric co-morbidities; 2) gastrointestinal features that may be associated with ASD, 3) candidate genes and genetic variation among individuals with ASD. and how they interact with environmental risk factors, 4) potential for parental infection, immune function, and autoimmunity to be associated with increased ASD risk, 5) potential for parental hormonal and reproductive characteristics to be associated with increased ASD risk, and 6) potential for sociodemographic and lifestyle factors to be associated with increased ASD risk. To address these goals, this study will conduct developmental assessments on the children and collect extensive data on the pre- and perinatal health and environment of the children and their parents via interviews, medical record review, and the collection of biologic samples. This large study of ASD will improve our understanding of how autism differs phenotypically from other disabilities and from typical development. It will also help identify potential risk factors for autism that deserve more attention. [unreadable] [unreadable] [unreadable]